Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis
| Autor: | Cathrin Gudd, Robert D. Goldin, Rooshi Nathwani, You Yone, Charalambos G. Antoniades, James Larkin, A. Dhar, Sujit Mukherjee, Tong Liu, Evangelos Triantafyllou, Lewis Au, Benjamin Shum, Lucia A. Possamai, Samra Turajlic, David J. Pinato, Kevin J. Woollard, Naveenta Kumar, Mark Thursz, Martin Gore, Wafa Khamri |
|---|---|
| Přispěvatelé: | Academy of Medical Sciences |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell 1117 Public Health and Health Services 03 medical and health sciences 0302 clinical medicine Immune system medicine Cytotoxic T cell immune checkpoint Gastroenterology & Hepatology Hepatology business.industry Monocyte 1103 Clinical Sciences Immunotherapy Granzyme B immunotherapy-related hepatitis 030104 developmental biology Cytokine medicine.anatomical_structure Cancer research 030211 gastroenterology & hepatology immunotherapy business CD8 |
| Zdroj: | Journal of Hepatology. 75:177-189 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2021.02.008 |
| Popis: | Background & Aims: Checkpoint inhibitor-related hepatitis (CPI-Hep) is an emerging clinical challenge. We aimed to gain insights into the immunopathology of CPI-Hep by comprehensively characterising myeloid and lymphoid subsets. Methods: CPI-treated patients with or without related hepatitis (CPI-Hep; n = 22 and CPI-noHep; n = 7) were recruited. Phenotypic and transcriptional profiling of peripheral immune subsets was performed and compared with 19 healthy controls (HCs). In vitro monocyte-derived macrophages (MoMFs) were assessed for activation and cytokine production. CD163, CCR2, CD68, CD3, CD8 and granzyme B expression was assessed using immunohistochemistry/immunofluorescence (n = 4). Results: A significant total monocyte depletion was observed in CPI-Hep compared with HCs (p = 0.04), along with a proportionate increase in the classical monocyte population (p = 0.0002) and significant upregulation of CCR2, CD163 and downregulation of CCR7. Soluble CD163 levels were significantly elevated in CPI-Hep compared with HCs (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect